MRC1 and colorectal carcinoma: In the context of MSI and an underlying (hereditary or sporadic) defect in MMR the use of 5-FU in MSI-H CRC merits particular attention: as demonstrated in numerous in vitro studies, inactivation of the MMR system can result in resistance, or rather tolerance (i.e., failure to induce cell-cycle arrest), to 5-FU treatment (4, 20).